PAGE CONTENTS

Complications

Myelodysplastic syndromes (MDS) are hematopoietic stem cell malignancies characterized by bone marrow failure and ineffective hematopoiesis. MDS may be associated with cytopenias and can also progress to acute myeloid leukemia (AML).¹ The main complications linked to MDS are the consequence of cytopenias and progression to AML.² Other complications include infections and pulmonary events.³ Most patients who have MDS die of complications without acquiring AML.⁴

Complications of Cytopenia

Anemia in MDS, which is due to ineffective erythropoiesis, is accompanied by mild hemolysis and low reticulocyte counts.⁵ Anemia is not a temporary manifestation of the disease but a chronic condition that worsens with time. Its effects are greater in patients with cardiac disease. Anemia increases mortality in older patients (>65 years) and causes a poor quality of life. Older patients may experience disability and decreased muscle strength.⁵

MDS is associated with thrombocytopenia and dysfunctional platelet activity. The defect most commonly reported is abnormal aggregation. Patients who require surgery or have bleeding problems may receive platelet transfusions. Life-threatening bleeding may develop in patients who are thrombocytopenic and have an infection.²

Read more about MDS surgical management

Inadequate erythropoiesis can lead to an increase in the intestinal absorption of iron and therefore to iron overload in patients with MDS and AML. The transfusion dependency of many patients can also lead to iron overload, which causes cellular and systemic changes and cell death due to the production of reactive oxygen species (ROS). Additionally, excessive iron in bone marrow and tissues may induce microenvironmental changes that cause bone marrow failure in patients with MDS and AML.^6,7

Excessive iron affects the immune system and increases susceptibility to infection. It also affects response to chemotherapy and the outcome of hematopoietic stem cell transplant (HSCT).⁶

In addition to iron overload, transfusion dependency may lead to cardiac events and shorten survival.⁸

Read more about MDS prognosis

Progression to Acute Myeloid Leukemia

AML that develops in association with a bone marrow disorder is secondary AML. Secondary AML accounts for up to 35% of all cases of AML, and most of these secondary cases (60% to 80%) are due to MDS progression. AML is diagnosed when the blast count is increased to 20% or more of all nucleated cells in the bone marrow.^6,9

In AML, limited hematopoietic cellular maturation results in an accumulation of myeloblasts in the blood or bone marrow. In contrast to what is observed in MDS, cell survival and proliferation are increased in AML.⁹

In comparison with patients in whom AML develops de novo, those with secondary AML have lower rates of complete remission, relapse-free survival, and overall survival.⁹

Read more about MDS life expectancy

Infectious Complications

Various studies have reported infectious complications of MDS,¹⁰ which are due mainly to neutropenia and a cause of morbidity and mortality. Few studies have reported on the bacterial agents responsible for the infections; however, Enterobacter species and coagulase-negative staphylococci are some of the implicated bacteria.⁷

In addition to neutropenia, immune-disorders, and iron overload, defective neutrophil function can increase the risk of infection in MDS. Among the qualitative defects in neutrophils that have been reported are reduced phagocytosis, production of oxygen intermediates, and decreased bactericidal and fungicidal activities.⁷

In a retrospective trial of 430 patients, sepsis, fever of unknown origin, and respiratory tract infections accounted for the deaths observed.¹⁰ Another study, which compared 2253 patients with MDS and more than 1 million individuals without MDS, showed that infection rates were higher in patients with MDS. The infectious complications identified were pneumonia, sepsis, bacteriemia, and skin infections.¹⁰

The increased risk of infectious diseases may be a consequence not only of the disease itself but also of the high doses of chemotherapy required for treatment.⁷

Read more about MDS risk factors

Noninfectious Pulmonary Complications

Noninfectious pulmonary complications observed in patients with MDS include³:

Diffuse infiltrating pneumonia related to acute immune vasculitis;
Sweet syndrome, characterized by skin lesions due to neutrophilic infiltration (visualized on chest radiographs) of the superficial dermis (red or purple papules on the upper limbs, head, and neck);
Hypereosinophilic syndrome;
Pulmonary alveolar proteinosis, characterized by the accumulation of surfactant-associated phospholipoproteinaceous material in alveoli and bronchioles;
Organizing pneumonia, characterized by nonspecific inflammation with alveolar opacities; and
Pulmonary arterial hypertension.

Read more about MDS care team

References

Volpe VO, Garcia-Manero G, Komrokji RS. Myelodysplastic syndromes: a new decade. Clin Lymphoma Myeloma Leuk. 2022;22(1):1-16. doi:10.1016/j.clml.2021.07.031
Tricot GJ. Complications and treatment of the myelodysplastic syndromes. Leuk Res. 1992;16(1):117-21. doi:10.1016/0145-2126(92)90110-s
Lamour C, Bergeron A. Non-infectious pulmonary complications of myelodysplastic syndromes and chronic myeloproliferative disorders. Rev Mal Respir. 2011;28(6):e18-e27. doi:10.1016/j.rmr.2009.04.001
Garcia-Manero G, Chien KS, Montalban-Bravo G. Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management. Am J Hematol. 2020;95(11):1399-1420. doi:10.1002/ajh.25950
Santini V. Anemia as the main manifestation of myelodysplastic syndromes. Semin Hematol. 2015;52(4):348-56. doi:10.1053/j.seminhematol.2015.06.002
Weber S, Parmon A, Kurrle N, Schnütgen F, Serve H. The clinical significance of iron overload and iron metabolism in myelodysplastic syndrome and acute myeloid leukemia. Front Immunol. 2021;11:627662. doi:10.3389/fimmu.2020.627662
Toma A, Fenaux P, Dreyfus F, Cordonnier C. Infections in myelodysplastic syndromes. Haematologica. 2012;97(10):1459-1470. doi:10.3324/haematol.2012.063420
Goldberg SL, Chen E, Corral M, et al. Incidence and clinical complications of myelodysplastic syndromes among United States Medicare beneficiaries. J Clin Oncol. 2010;28(17):2847-52. doi:10.1200/JCO.2009.25.2395
Menssen AJ, Walter MJ. Genetics of progression from MDS to secondary leukemia. Blood. 2020;136(1):50-60. doi:10.1182/blood.2019000942
Radsak M, Platzbecker U, Schmidt CS, Hofmann WK, Nolte F. Infectious complications in patients with myelodysplastic syndromes: a review of the literature with emphasis on patients treated with 5-azacitidine. Eur J Haematol. 2017;99(2):112-118. doi:10.1111/ejh.12883

Reviewed by Kyle Habet, MD, on 6/16/2023.

Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.

Myelodysplastic Syndromes (MDS)